A Phase 3, Randomized, Multicenter, Open-Label, Controlled Study to Evaluate the Efficacy and Safety of Pegcetacoplan (APL-2) in Patients with Paroxysmal Nocturnal Hemoglubinuria (PNH)
A Phase 3, Randomized, Multicenter, Open-Label, Controlled Study to Evaluate the Efficacy and Safety of APL-2 in Patients with Paroxysmal Nocturnal Hemoglubinuria (PNH)
This is a prospective, randomized, multi-center, open-label, controlled study. Following screening, subjects will complete biweekly (biw) visits from Week 0 to Week 26. Subjects will be randomized either to APL-2 or Standard of Care (SOC) (excluding complement inhibitors). Subjects randomized to the SOC (excluding complement inhibitors) treatment arm may receive APL-2 escape therapy if their Hb level drops ≥2 g/dL below their Baseline value.
APL-2 infusion is a solution of APL-2 in acetate-buffered sorbitol for subcutaneous (SC) administration. A bifurcated line will be utilized to administer the 20mL APL-2 infusion allowing the volume to be distributed across the 2 separate injection sites in order to reduce patient discomfort.
The FreedomEdge Pump will be utilized as the drug delivery system is a spring based, fully mechanical “syringe driver” providing a constant force to advance the plunger of a filled syringe, displacing the fluid through the infusion sets to the patient’s subcutaneous tissue. If pressure at the infusion sites increases (caused by tissue saturation), the system immediately responds by automatically slowing down to help prevent pain and swelling.
The infusion set and bifurcated needles have been used in an ongoing study (APL2-101) in healthy subjects. In addition, the 20 mL volume of APL-2 is currently being administered using the infusion set and the bifurcated needles in 5 PNH subjects in ongoing clinical studies
|2017 - 2022||Research to enhance and extend healthy lives||Non-communicable diseases|
|Start Date||Duration in Months||Target Completion Date||Actual Completion Date|
|Apellis Pharmaceuticals, Inc.||Private Business||United States of America||3000002140826|
|Novotech (Australia) Pty. Ltd. - Philippine Branch||Private Business||NCR||3000002140826|
|Apellis Pharmaceuticals, Inc.||United States of America|
|Name||Institution and Institution Address|
|Jennifer Olive Arellanofirstname.lastname@example.org||1604|
|Name||Institution and Institution Address|
|Federico Grossi, MD., PHDemail@example.com||40014|
|Catherine Rosales, MD||Principal Investigator||The Medical City|
|Jasmin Igama, MD||Principal Investigator||Baguio General Hospital and Medical Center|
|Lynda Mae P. Lepatan, MD||Principal Investigator||Perpetual Succour Hospital|
|Narcisa Sonia Comia, MD||Principal Investigator||Mary Mediatrix Medical Center|
|Priscilla B. Caguioa, MD||Principal Investigator||St. Luke's Medical Center - Quezon City|
|Teresita Dumagay, MD||Principal Investigator||Makati Medical Center|
|Project Location||Institutional Ethics Review Board|
|The Medical City||The Medical City - Institutional Review Board|
|Baguio General Hospital and Medical Center||Baguio General Hospital and Medical Center Ethics Review Committee|
|Perpetual Succour Hospital||Perpetual Succour Hospital Institutional Ethics and Review Board|
|Mary Mediatrix Medical Center||Mary Mediatrix Medical Center Research Ethics Review Committee|
|St. Luke's Medical Center - Quezon City||St. Luke's Medical Center Institutional Ethics Review Board|
|Makati Medical Center||Makati Medical Center Institutional Review Board|
This proposed Phase 3 study is to further evaluate treatment efficacy and safety of APL-2 as monotherapy in patients with Pyroxysmal Nocturnal Hemoglubinuria (PNH).
The primary objective of this study is to evaluate the efficacy of APL-2, compared to SOC (excluding complement inhibitors), in patients with PNH, as assessed by:
• Hemoglobin stabilization defined as avoidance of a > 1 g/dl decrease in Hb levels from Baseline in the absence of transfusion through Week 26 (Yes/No)
• Reduction in lactate dehydrogenase (LDH) level from Baseline to Week 26
Secondary objectives of this study are:
• To evaluate the efficacy of APL-2, compared to SOC (excluding complement inhibitors), as assessed by:
o Hemoglobin response (Yes/No) in the absence of transfusions (Hb response is defined as a ≥1g/dL increase in Hb from Baseline at Week 26)
o Change from Baseline to Week 26 in absolute reticulocyte count
o Change from Baseline to Week 26 in Hb level
o Number of packed red blood cell (PRBC) units transfused from Baseline to Week 26
o Change from Baseline to Week 26 in Functional Assessment of Chronic Illness Therapy- (FACIT-) Fatigue Scale score
o Normalization of Hb levels (defined as ≥1xULN) from Baseline to Week 26 in the absence of transfusions (Yes/No)
o Normalization of LDH levels ≤1 x the upper limit of normal (ULN) from Week 4 to Week 26 (Yes/No)
o Change from Baseline to Week 26 in European Organization for Research and Treatment of Cancer (EORTC) 30-item Core Quality of Life Questionnaire (QLQ-C30) scores (version 3)
o Change from Baseline to Week 26 in Linear Analog Assessment (LASA) scale scores
o Change from Baseline to Week 26 in LDH level
o Absolute reticulocyte count normalization (o Time to failure of Hb stabilization
o Time to transfusion
• To evaluate the safety of APL-2 as assessed by:
o Incidence and severity of treatment-emergent adverse events (TEAEs)
o Incidence of thromboembolic events
o Changes from Baseline in laboratory parameters
o Changes from Baseline in electrocardiogram (ECG) parameters
o Incidence of anti-APL2 antibodies
- Hong Kong
16 Sep 2019
1. Be at least 18 years old (inclusive).
2. Have LDH ≥1.5 x ULN at the screening visit.
3. Have PNH diagnosis, confirmed by high sensitivity flow cytometry (granulocyte or monocyte clone >10%).
4. Have Hb less than the lower limit of normal (LLN) at the screening visit.
5. Have ferritin greater than/equal to the LLN, or total iron binding capacity (TIBC) less than/equal to ULN at the screening visit, based on central laboratory reference ranges. If a subject is receiving iron supplements at screening, the Investigator must ensure that the subject’s dose has been stable for 4 weeks prior to screening, and it must be maintained throughout the study. Subjects not receiving iron at screening must not start iron supplementation during the course of the study.
6. Body mass index (BMI) ≤ 35 kg/m2 at the screening visit.
7. Have a platelet count of >50,000/mm3 at the screening visit.
8. Have an absolute neutrophil count >500/mm3 at the screening visit.
9. Women of child-bearing potential (WOCBP) must have a negative pregnancy test at screening, and must agree to use protocol-defined methods of contraception for the duration of the study and for 90 days after their last dose of study drug.
10. Males must agree to use protocol-defined methods of contraception, and agree to refrain from donating sperm for the duration of the study and for 90 days after their last dose of study drug.
11. Have vaccination against Streptococcus pneumoniae, Neisseria meningitides (types A, C, W, Y, and B), and Haemophilus influenzae (type B) either within 2 years prior to Day 1 dosing, or agree to receive vaccination 14 days after starting treatment with APL-2 (along with prophylactic antibiotic therapy for at least the 14 days between APL-2 treatment initiation and vaccination and 14 days post vaccination). Vaccination is mandatory, unless documented evidence exists that subjects are non-responders to vaccination (as evidenced by titers or display titer levels within acceptable local limits).
12. Be willing and able to give informed consent.
1. Treatment with any complement inhibitor (eg, eculizumab) within 3 months prior to screening.
2. Hereditary complement deficiency.
3. History of bone marrow transplantation.
4. Concomitant use of any of the following medications is prohibited if not on a stable regimen for the time period indicated below prior to screening:
• Erythropoietin or immunosuppressants for at least 8 weeks
• Systemic corticosteroids for at least 4 weeks
• Vitamin K antagonists (eg, warfarin) with a stable international normalized ratio (INR) for at least 4 weeks
• Iron supplements, vitamin B12 or folic acid for at least 4 weeks
• Low-molecular-weight heparin for at least 4 weeks
5. History or presence of hypersensitivity or idiosyncratic reaction to compounds related to the investigational product or SC administration.
6. Participation in any other investigational drug trial or exposure to other investigational agent, device, or procedure within 30 days or 5 half-lives, whichever is longer.
7. Planning to become pregnant or currently a breast-feeding woman.
8. History of meningococcal disease.
9. Any comorbidity or condition (such as malignancy) that, in the opinion of the Investigator, could put the subject at increased risk or potentially confound study data.
APL-2 infusion (drug product) is a solution of APL-2 in 5% dextrose or a solution of APL-2 in acetate-buffered mannitol or a solution of APL-2 in acetate-buffered sorbitol for subcutaneous (SC) administration. APL-2 is being developed for the treatment of PNH.
|2020-11-04||Amendments related to the protocol||-Changed APL-2 to pegcetacoplan, added COVID-19 safety activities, added statement regarding understanding/agreement of subject that study related data maybe transferred in an electronic secured file to be shared to Sponsor/representative who will review it and ensuring that personal information is concealed|
This is a 2-arm, controlled study comparing APL-2 administration against standard of care (SOC) for patients with PNH.
The SOC arm will exclude any concurrent or recent (within 3 months) use of complement inhibitors.